Upadacitinib Achieves Top-line Results in Phase 2b Atopic Dermatitis Study

The investigational drug upadacitinib achieved positive top-line results in a phase 2b study for the treatment of patients with moderate-to-severe atopic dermatitis inadequately controlled by topical treatments.

Upadacitinib is a once-daily oral agent designed to selectively inhibit JAK1, which plays a key role in the pathophysiology of immune-mediated inflammatory disorders, according to a press release.

“We are excited by the results of this study, which show that upadacitinib has the potential to be an important treatment option for patients with atopic dermatitis,” Michael Severino, MD, executive vice president of research and development and chief scientific officer at AbbVie, said in the release.

The randomized, double-blind, parallel-group, placebo-controlled, multicenter phase 2b study is an 88-week ongoing trial designed to evaluate the safety and efficacy of upadacitinib in adult patients with moderate-to-severe atopic dermatitis inadequately controlled by topical treatments, or in patients for whom topical treatments were not medically advisable.

Participants were randomized in a 1:1:1:1 ratio to either receive 30 mg of upadacitinib, 15 mg of upadacitinib, 7.5 mg of upadacitinib, or placebo.

The primary endpoint was mean percentage change in Eczema Area and Severity Index (EASI) score at 16 weeks compared with placebo. Key secondary endpoints included the proportion of patients who achieved EASI 90, EASI 75, an Investigator Global Assessment of 0 or 1 and percent change in pruritus/itch numerical rate scale from baseline to week 16 compared with placebo.

At week 16, across all doses, patients treated with upadacitinib achieved statistically significant improvement in the primary and all skin and itch secondary endpoints, compared with placebo. Furthermore, itch reduction was observed within the first week and improvement in skin within the first 2 weeks across all doses, according to the release.

The mean percent change from baseline in the EASI score, a measure of the extent and severity of atopic dermatitis and the primary endpoint in this study, was 74/62/39 percent for patients receiving the 30/15/7.5 mg doses of upadacitinib, respectively, compared to 23 percent for patients receiving placebo (p<0.001/0.001/0.05, respectively). EASI 90 was achieved by 50%, 26% and 14% of patients, respectively, compared with 2% of patients receiving placebo.

Clear or almost clear skin was achieved by 50%, 31%, and 14% of patients receiving the 30/15/7.5 mg doses of upadacitinib compared with 2% of patients in the placebo arm. Significant improvement in pruritus was observed in 69%, 48%, and 40% of patients, respectively.

The most common adverse events (AEs) were upper respiratory tract infection, atopic dermatitis, and acne. No reports of herpes zoster, malignancies, deaths, or cases of pulmonary embolism or deep vein thrombosis were observed.

There were no new safety signals detected in the phase 2b study. The safety profile of upadacitinib will be further evaluated in the phase 3 trial.

“We look forward to advancing upadacitinib to phase 3 studies in 2018,” Severino said in the release. “AbbVie’s continued progress across our upadacitinib clinical development program further demonstrates that selective inhibition of the JAK1 pathway may be a novel therapeutic approach across a broad range of immune-mediated diseases.”